Updated on 2022/11/01


Advanced Science Research Center Special-Appointment Assistant Professor
Special-Appointment Assistant Professor
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  • Ph.D. ( 2018.3   Okayama University )

Research Interests

  • トランスポーター

Research Areas

  • Life Science / Pharmaceutical hygiene and biochemistry



  • Vesicular nucleotide transporter is a molecular target of eicosapentaenoic acid for neuropathic and inflammatory pain treatment. Reviewed International journal

    Yuri Kato, Kengo Ohsugi, Yuto Fukuno, Ken Iwatsuki, Yuika Harada, Takaaki Miyaji

    Proceedings of the National Academy of Sciences of the United States of America   119 ( 30 )   e2122158119   2022.7

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    Language:English   Publishing type:Research paper (scientific journal)  

    Eicosapentaenoic acid (EPA), an omega-3 (ω-3) polyunsaturated fatty acid, is an essential nutrient that exhibits antiinflammatory, neuroprotective, and cardiovascular-protective activities. Although EPA is used as a nutrient-based pharmaceutical agent or dietary supplement, its molecular target(s) is debatable. Here, we showed that EPA and its metabolites strongly and reversibly inhibit vesicular nucleotide transporter (VNUT), a key molecule for vesicular storage and release of adenosine triphosphate (ATP) in purinergic chemical transmission. In vitro analysis showed that EPA inhibits human VNUT-mediated ATP uptake at a half-maximal inhibitory concentration (IC50) of 67 nM, acting as an allosteric modulator through competition with Cl-. EPA impaired vesicular ATP release from neurons without affecting the vesicular release of other neurotransmitters. In vivo, VNUT-/- mice showed a delay in the onset of neuropathic pain and resistance to both neuropathic and inflammatory pain. EPA potently attenuated neuropathic and inflammatory pain in wild-type mice but not in VNUT-/- mice without affecting the basal nociception. The analgesic effect of EPA was canceled by the intrathecal injection of purinoceptor agonists and was stronger than that of existing drugs used for neuropathic pain treatment, with few side effects. Neuropathic pain impaired insulin sensitivity in previous studies, which was improved by EPA in the wild-type mice but not in the VNUT-/- mice. Our results showed that VNUT is a molecular target of EPA that attenuates neuropathic and inflammatory pain and insulin resistance. EPA may represent a unique nutrient-based treatment and prevention strategy for neurological, immunological, and metabolic diseases by targeting purinergic chemical transmission.

    DOI: 10.1073/pnas.2122158119



  • Vesicular nucleotide transporter mediates ATP release and migration in neutrophils Reviewed

    Yuika Harada, Yuri Kato, Takaaki Miyaji, Hiroshi Omote, Yoshinori Moriyama, Miki Hiasa

    Journal of Biological Chemistry   293 ( 10 )   3770 - 3779   2018.3

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    Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1074/jbc.m117.810168


  • Vesicular Polyamine Transporter Mediates Vesicular Storage and Release of Polyamine from Mast Cells Reviewed

    Tomoya Takeuchi, Yuika Harada, Satomi Moriyama, Kazuyuki Furuta, Satoshi Tanaka, Takaaki Miyaji, Hiroshi Omote, Yoshinori Moriyama, Miki Hiasa

    Journal of Biological Chemistry   292 ( 9 )   3909 - 3918   2017.3

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    Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1074/jbc.m116.756197


  • Identification of a mammalian vesicular polyamine transporter Reviewed

    Miki Hiasa, Takaaki Miyaji, Yuka Haruna, Tomoya Takeuchi, Yuika Harada, Sawako Moriyama, Akitsugu Yamamoto, Hiroshi Omote, Yoshinori Moriyama

    Scientific Reports   4 ( 1 )   2014.10

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    Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    DOI: 10.1038/srep06836


    Other Link: http://www.nature.com/articles/srep06836

  • Immunological Identification of Vesicular Nucleotide Transporter in Intestinal L Cells Reviewed

    Yuika Harada, Miki Hiasa

    Biological and Pharmaceutical Bulletin   37 ( 7 )   1090 - 1095   2014

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    Publishing type:Research paper (scientific journal)   Publisher:Pharmaceutical Society of Japan  

    DOI: 10.1248/bpb.b14-00275